The FASEB Summer Research Conference on Ubiquitin and Cellular Regulation is the premier forum for the field on the fundamental biochemistry and biologic functions of the ubiquitin-proteasome system. This conference has been held biannually since 1989, always at Vermont Academy, and always supported by FASEB. This application seeks support for the next three conferences (2012, 2014, 2016). The biological functions of ubiquitin require its covalent attachment to cellular proteins, and the best-studied consequence of this is degradation by the 26S proteasome. Recent discoveries have begun to reveal the structural basis for ubiquitin activation and conjugation reactions, as well as the complex steps involved in translocating target proteins into the proteasome for degradation. Understanding these processes is critical, as the selective degradation of proteins by the ubiquitin system is a mechanism for control of virtually all aspects of eukaryotic cell biology, including the cell cycle, transcription, metabolic pathways, development, and antigen processing. Furthermore, defects or hyperactivation of the system is involved in many disease processes, particularly cancer, neurologic, and metabolic diseases. In addition to functioning as a degradation signal, ubiquitination has non- proteolytic functions in protein trafficking and signaling, and this aspect of the pathway is critical for processes that involve membrane receptors and signaling in the innate immune system. Beyond ubiquitin, itself, there are several ubiquitin-like proteins that are conjugated through parallel biochemical pathways, and the characterization of the biologic functions of these proteins is a very active area of discovery. These pathways are also critical in infectious diseases, as it is now evident that microbes encode ubiquitin-like proteins, that bacteria and viruses produce enzymes to modulate cellular ubiquitination pathways in host cells, and that cells defend themselves against infectious agents with specific ubiquitin-like proteins. The 2012 meeting will be held from June 24-29, and the organizers are Jon Huibregtse (Univ. of Texas) and Randy Hampton (UC-San Diego). The conference will begin with a key-note presentation by Dr. Dan Finley (Harvard Medical School), and will be followed by nine scientific sessions covering, each chaired by leaders in field (5 women, 4 men). So far, 28 internationally renowned speakers have been confirmed (16 women, 2 minorities). Approximately 10 additional speakers will be chosen from abstracts, and we will continue to seek diversity among these speakers and among attendees, in general. Overall, we seek to enhance the dissemination of new and exciting findings in this dynamic field, which will broaden our understanding of the roles of ubiquitin, the proteasome, and ubiquitin-like proteins in health and disease. PUBLIC HEALTH RELEVANCE: This conference will be focused on the importance of protein ubiquitylation, protein turnover, and modification by ubiquitin-related proteins in many disease states, including cancer, neurologic and developmental diseases, and viral and microbial infectious diseases. We anticipate that exciting developments will be presented on the identification of pharmacologic agents that modulate the activities of ubiquitin/Ubl pathway enzymes and the proteasome.